The coronary microcirculation plays a critical role in normal cardiac physiology as well as in many disease states. However, methods to evaluate the function of the coronary microvessels have been limited by technical and theoretical issues. Recently, the index of microcirculatory resistance (IMR) has been proposed and validated as a simple and specific invasive method of assessing the coronary microcirculation. By relying on the thermodilution theory and using a pressure-temperature sensor guidewire, IMR provides a measurement of the minimum achievable microcirculatory resistance in a target coronary artery territory, enabling a quantitative assessment of the microvascular integrity. Unlike indices such as coronary flow reserve, IMR is highly reproducible and independent of hemodynamic changes. In ST-elevation myocardial infarction, IMR predicts myocardial recovery and long-term mortality, whereas in patients with stable coronary artery disease, preintervention IMR predicts the occurrence of periprocedural myocardial infarction. Increasingly, research has focused on IMR-guided interventions of the microcirculation, with the aim of preventing and/or treating the microcirculatory dysfunction that commonly accompanies the epicardial coronary disease. In the present review, we will discuss the theoretical and practical basis for IMR, the clinical studies supporting it, and the future lines of research using this novel tool.